Optical Coherence Tomography (OCT) is a technology for performing high-resolution cross sectional imaging that can provide images of tissue structure on the micron scale in situ and in real time. OCT is a method of interferometry that uses light containing a range of optical frequencies to determine the scattering profile of a sample. The axial resolution of OCT is inversely proportional to the span of optical frequencies used.
In recent years, it has been demonstrated that frequency domain OCT has significant advantages in speed and signal to noise ratio as compared to time domain OCT (Leitgeb, R. A., et al., Optics Express 11:889-894; de Boer, J. F. et al., Optics Letters 28: 2067-2069; Choma, M. A., and M. V. Sarunic, Optics Express 11: 2183-2189).
In frequency domain OCT, a light source capable of emitting a range of optical frequencies excites an interferometer, the interferometer combines the light returned from a sample with the light returned from a reference reflector, and the intensity of the combined light is recorded as a function of optical frequency to form an interference spectrum. A Fourier transform of the interference spectrum provides the reflectance distribution along the depth within the sample. Frequency domain OCT requires some means to record the interference spectrum, the intensity of light output from the interferometer as a function of optical frequency. Current methods of Frequency domain OCT can be divided into two categories.
In spectral-domain OCT, a grating or prism or other means is used to disperse the output of the interferometer into its optical frequency components. The intensities of these separated components are measured using an array of optical detectors, each detector receiving an optical frequency or a fractional range of optical frequencies. The set of measurements from these optical detectors forms an interference spectrum (Smith, L. M. and C. C. Dobson, Applied Optics 28: 3339-3342). Typically the light source emits a broad range of optical frequencies simultaneously.
Alternatively, in swept-source OCT, the interference spectrum is recorded by using a source with adjustable optical frequency, with the optical frequency of the source swept through a range of optical frequencies, and recording the interfered light intensity as a function of time during the sweep (Swanson, E, et al., U.S. Pat. No. 5,321,501).
Frequency-domain OCT efficiently uses the light returned from a range of depths within the sample, as all the returned light contributes to the modulation in the interference spectrum. This is in contrast to the case of time domain OCT, in which the interference signal is sensitive only to light returned from depths in the sample that match the current length of the reference arm to within the coherence length of the source. For a given illumination level and time of exposure, the achievable signal to noise ratio is substantially greater in frequency-domain OCT than in time-domain OCT (Leitgeb, R. A. et al., Optics Express 11: 889-894; de Boer, J. F. et al., Optics Letters 28: 2067-2069; Choma, M. A., and M. V. Sarunic, Optics Express 11: 2183-2189).
Chromatic dispersion is a property of an optical element that characterizes the degree by which the optical path length through that element varies across a range of optical frequencies. OCT determines the position in the sample of a scattering center based on the difference in optical group delay between two optical paths: 1) the path of light scattered from the sample, and 2) a reference optical path. Most OCT literature refers simply to the difference between sample and reference optical path lengths; but when one considers chromatic dispersion one must distinguish between the phase delay and the group delay associated with a given optical path length. OCT is sensitive to the difference in group delay (see, for example, section 2.1 in Fercher et al., Optics Express 9: 610-615). OCT necessarily uses a range of optical frequencies. If the chromatic dispersion is not matched between the two paths, the apparent position of the scattering center depends on the optical frequency used. A mismatch in chromatic dispersion thus broadens the axial resolution of the OCT as explained by Hitzenberger et al., (Journal of Biomedical Optics 4: 144-151). For this reason, in most OCT systems the chromatic dispersion is closely matched between sample and reference paths (see, for example, U.S. Pat. Nos. 6,385,358, 6,615,072, 6,618,152) sometimes through the use of dispersive optical devices (see, for example U.S. Pat. No. 6,282,011). One of the advantages of quantum OCT (a method of time-domain OCT described by Teich et al. in U.S. Pat. No. 6,882,431) is that it partially cancels the mismatch in chromatic dispersion between the sample and reference paths.
Since a perfect match of chromatic dispersion is not simple and can add cost to a frequency domain OCT system, numerical correction of the residual mismatch in chromatic dispersion has been described by Fercher et al. (Optics Express 9: 610-615; Optics Communications 204: 67-74) and by Marks et al. (Applied Optics 42: 204-217). The preceding authors used a test sample to determine the residual mismatch in chromatic dispersion. Alternatively, the numerical correction for dispersion can be empirically adjusted for best sharpness of the resulting OCT image, without using a test sample, as described by Wojtkowski et al. (Optics Express 12: 2404-2422).
Frequency domain methods of OCT use the fact that interference between light scattered from the sample and the reference beam causes spectral interference fringes, a modulation in the intensity of the combined beam as a function of optical frequency. The spacing of the interference fringes depends on the difference in optical group delay between the light scattered from the sample, and reference light. In addition to chromatic dispersion match or correction, there are two additional major issues associated with this method.
The first one is that the spacing of the interference fringes does not depend on which of the two paths is longer. Therefore, simple methods of frequency-domain OCT do not distinguish between scattering from a sample location corresponding to an optical group delay a certain amount longer than that of the reference path, and scattering with an optical group delay the same amount shorter than that of the reference path. The resulting image contains the true scattering profile plus the superposed mirror image of the scattering profile. (See, for example, Yun et al., Optics Express 12:4822-4828.)
Phase shifting one of the interfering beams has been proposed to remove the mirror image in spectral domain OCT, but to date these methods leave some residual image and are complicated and costly (Leitgeb, R. A. et al., Optics Letters 28: 2201-2203; Izatt et al. U.S. Patent Publication No. 2004/0239938; co-pending U.S. patent application Ser. No. 10/933,795; Sarunic, et al., SPIE 5316: 241-247). In particular, sequential phase shift does not produce a good result if the sample such as a human eye tends to move during the period when the multiple phase interference spectrums are recorded (Targowski et al., Optics Communications, 229:79-84). On the other hand, simultaneous parallel multi-phase detection of the interference spectrum would require the use of at least two spectrometers or two detector arrays in the spectrometer, which will not only add complication in terms of optical alignment but also substantially increase the spectrometer cost. Frequency shifting one of the interfering beams in swept-source OCT has been used to shift the image away from its mirror image (Yun et al., Optics Express 12: 4822-4828), but this method is applicable only in situations where the sample being imaged has finite visible extent, and in which the detection electronics can accept the resulting higher-frequency signal. In addition, it requires an additional optical frequency shifter which is an expensive item and hence would add cost to the OCT system.
The second issue is that when the interference spectrum is recorded as a function of optical frequency, periodic interfering signals as a function of optical frequency can corrupt the digitized spectrum. For example, in the case of spectral-domain OCT, the readout electronics of the array detector often adds periodic pattern noise to the recorded optical intensities. In swept-source OCT, electronic clocks and counters can add a similar periodic error signal. Furthermore, a spectral ripple of the light source, such as those caused by etalon effects from inadvertent reflections in path from the light source, causes a periodic error signal in the recorded interference spectrum.
The periodic error signal from these and similar sources is difficult to distinguish from the interference fringes caused by light scattered from the sample. If present in the spectra when the image is reconstructed, the periodic error signal will cause the artificial appearance of a scattering center at a particular depth in the reconstructed image. The periodic error signal can be partially removed by measuring it separately from the measurement on the sample, and subtracting them from measurements on the sample. Such correction methods work only to the extent that the periodic error signal repeats exactly, in both amplitude and phase, on each spectrum acquisition. Signals from non-synchronized clocks, for example, will not repeat exactly and cannot be cancelled in this way.
From the above discussions, it can be seen that previous frequency-domain OCT systems generally require a match in the chromatic dispersion characteristics of the two interferometer paths and even with a perfect match or a correction of the residual mismatch, the existing methods cannot cost-effectively address the issue of a mirror image and the artifacts induced by periodic spectral noise from either the source or the detector, there is hence a need in the art of frequency domain OCT to remove the stringent requirement of chromatic dispersion match, to easily and clearly distinguish the mirror image from the real image and to substantially suppress the image artifacts due to periodic spectral error signals.